From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:235d.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:235d.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_235d| PDB=235d | SCENE= }} | | {{STRUCTURE_235d| PDB=235d | SCENE= }} |
| | | | |
| - | '''CRYSTAL STRUCTURE OF FOUR MORPHOLINO-DOXORUBICIN ANTICANCER DRUGS COMPLEXED WITH D(CGTACG) AND D(CGATCG): IMPLICATIONS IN DRUG-DNA CROSSLINK'''
| + | ===CRYSTAL STRUCTURE OF FOUR MORPHOLINO-DOXORUBICIN ANTICANCER DRUGS COMPLEXED WITH D(CGTACG) AND D(CGATCG): IMPLICATIONS IN DRUG-DNA CROSSLINK=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Among the new generations of anthracycline drugs, morpholino-doxorubicin (MDox) and its derivative have unusually potent activity when compared with the parent doxorubicin. 3"-Cyano-morpholino-doxorubicin (CN-MDox) has been suggested to form a covalent crosslink to DNA, although the exact mode of interactions remains unclear. To establish the structural basis of this crosslink, we carried out X-ray diffraction analyses of the complexes between four different morpholino-doxorubicins (i.e., MDox, CN-MDox, (R)- and (S)-2"-methoxy-morpholino-Dox (MMDox)) and two DNA hexamers CGTACG and CGATCG. Their crystal data are similar to other Dau/Dox complexes with space group P4(1)2(1)2,a = b approximately 28 A, c approximately 53 A. The refined structures at approximately 1.8 A resolution revealed that two drug molecules bind to the duplex with the aglycons intercalated between the CpG steps with their N3'-morpholino-daunosamines in the minor groove. The morpholino moiety is flexible and may adopt different conformations dependent on the sequence context. The O1" atoms of the two morpholino groups in the drug-DNA complexes are in van der Waals contact. The structural results suggest possible crosslinking mechanism of CN-MDox. It is worth pointing out that by linking two piperazinyl- or piperidinyl-doxorubicins at the 1" positions a new type of bis-doxorubicin derivatives may be synthesized which may bind to a hexanucleotide sequence with some specificity.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8527023}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8527023 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_8527023}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 25: |
Line 29: |
| | [[Category: Double helix]] | | [[Category: Double helix]] |
| | [[Category: Right handed dna]] | | [[Category: Right handed dna]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:21:26 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 23:39:03 2008'' |
Revision as of 20:39, 28 July 2008
Template:STRUCTURE 235d
CRYSTAL STRUCTURE OF FOUR MORPHOLINO-DOXORUBICIN ANTICANCER DRUGS COMPLEXED WITH D(CGTACG) AND D(CGATCG): IMPLICATIONS IN DRUG-DNA CROSSLINK
Template:ABSTRACT PUBMED 8527023
About this Structure
Full crystallographic information is available from OCA.
Reference
Crystal structures of four morpholino-doxorubicin anticancer drugs complexed with d(CGTACG) and d(CGATCG): implications in drug-DNA crosslink., Gao YG, Wang AH, J Biomol Struct Dyn. 1995 Aug;13(1):103-17. PMID:8527023
Page seeded by OCA on Mon Jul 28 23:39:03 2008
